miR-199b-5p-Stonin 2 axis regulates metastases and epithelial-to-mesenchymal transition of papillary thyroid carcinoma.

Papillary thyroid carcinoma is one of the most fatal malignant endocrine tumors, and the prognosis remains poor because of the lack of effective therapeutic targets. In this study, we demonstrated that the level of miR-199b-5p was markedly downregulated in papillary thyroid carcinoma. The ectopic expression level of miR-199b-5p in papillary thyroid carcinoma cell B-CPAP could inhibit growth, migration, and invasion as well as epithelial-mesenchymal transition (EMT) and decreased cell metastasis in vivo, but silencing miR-199b-5p caused a contradictory outcome. Additionally, Stonin 2 (STON2) was identified as a direct target gene of miR-199b-5p. Consistent with the downregulation of miR-199b-5p, the overexpression of STON2 induced the growth, migration and invasion of B-CPAP cells. It was also demonstrated that miR-199b-5p suppressed papillary thyroid carcinoma cell aggressiveness by targeting STON2. Furthermore, the overexpression of miR-199b-5p inhibited cell proliferation, promoted apoptosis, and increased the chemo-sensitivity of thyroid carcinoma B-CPAP cells toward the chemotherapy drug paclitaxel. Finally, in vivo experiments further demonstrated that miR-199b-5p suppressed tumor growth in nude mice. Thus, this study revealed that miR-199b-5p functions as antioncogene miRNA in papillary thyroid carcinoma cells and that the miR-199b-5p/STON2 axis might be a potential treatment option for papillary thyroid carcinoma. © 2018 IUBMB Life, 71(1):28-40, 2019.

Effects of water extracts of Rehmannia glutinosa on antioxidant system of Nrf2 in paraquat-induced insulin resistance diabetic rat model.

The objective of this study was to observe the effects of water extracts of Rehmannia glutinosa on the antioxidant system of Nrf-2 in diabetic mice induced by paraquat, and to provide the basis for its further development. Thirty male mice were randomly divided into the control group, model group and observation group. The mice in the model group and the observation group were treated with paraquat to induce insulin resistance, with the control group injected with the same volume saline. After the model establishment, the mice in observation group was given 1.2 g/kg·day with water extract of Rehmannia glutinosa, and the other groups were given equal volume of 1% hydroxymethyl cellulose sodium. After 7 days, the glucose tolerance was detected and the body weight was measured before and after the treatment. The body weight of the mice in the model group was significantly decreased (P<0.05), but the body weight of mice in the observation group was significantly higher than that in the model group (P<0.05). After 7 days of model establishment, the glucose tolerance of mice was damaged, with the blood sugar increased, but the level of blood sugar was significantly decreased when treated with water extracts of Rehmannia glutinosa. The water extract of Rehmannia glutinosa increased the level of phosphorylation of PKB significantly compared to the model group with the inhibition of PTEN. The level of malondialdehyde in mitochondria and muscle tissue was significantly increased after treated with water extracts of Rehmannia glutinosa (P<0.05). With decreased NQO-1 protein expression and the nuclear translocation of Nrf-2 in the model group, the water extract of Rehmannia glutinosa cloud reverse the injury effectively. Similarly, the water extract of Rehmannia glutinosa significantly increased the expression of IКBα, which was significantly decreased in the model group. In conclusion, water extracts of Rehmannia glutinosa effectively reversed the glucose metabolism disorder in insulin resistance mice induced by paraquat, and effectively activated the level of Nrf-2 to enhance the muscle insulin signal while alleviating the insulin resistance in mice.

IL-17RB enhances thyroid cancer cell invasion and metastasis via ERK1/2 pathway-mediated MMP-9 expression.

IL-17RB, a member of the IL-17 receptor family that can be activated by IL-17B, has been proved to be involved in inflammatory diseases and cancers. However, the function of IL-17RB in thyroid cancer is still unknown. In this study, IL-17RB expression in thyroid cancer cell lines and tissues was examined by real-time PCR and western blot. The effects of IL-17RB on cell invasion and migration were determined by in vitro invasion and migration assays, while the effects of IL-17RB on cell metastasis were analyzed by in vivo experiments. The results showed that IL-17RB expression was upregulated in both thyroid cancer cells and tissues. IL-17B dose-dependently promoted the invasion, growth and migration of thyroid cancer cells, whereas knockdown of IL-17RB attenuated the effects of IL-17B in vitro. Moreover, IL-17RB was involved in the metastasis and growth of thyroid cancer cells in vivo. In addition, IL-17RB induced ERK1/2 activation and increased MMP-9 expression in vitro and in vivo. Inhibition of ERK1/2 pathway blocked the IL-17RB-mediated thyroid cancer cell invasion and MMP-9 expression. Together, our findings demonstrate that IL-17RB can enhance thyroid cancer cell invasion and metastasis via ERK1/2 pathway-mediated MMP-9 expression, suggesting that IL-17RB may act as a potential therapeutic target for thyroid cancer therapy.